In sample analysis instrumentation, especially in separation systems such as liquid chromatography and capillary electrophoresis systems, smaller dimensions will generally result in improved performance characteristics and at the same time result in reduced production and analysis costs. Miniaturized separation systems provide more effective system design, result in lower overhead due to decreased instrumentation sizing and additionally enable increased speed of analysis, decreased sample and solvent consumption and the possibility of increased detection efficiency.
The conventional approach in miniaturization technology for liquid phase analysis is to use drawn fused-silica capillary. An evolving approach is to use silicon micromachining. To enable even greater reduction in separation system sizes, there has been a trend towards providing planarized systems having capillary separation microstructures. Production of miniaturized separation systems involving fabrication of microstructures in silicon by micromachining or microlithographic techniques has been described. Such techniques can include processes such as ithography, molding, and etching. See, e.g. Fan et al., Anal. Chem. 66(1):177-184 (1994); Manz et al., Adv. in Chrom. 33:1-66 (1993); Harrison et al., Sens. Actuators, B B10(2):107-116 (1993); Manz et at., Trends Anal. Chem. 10(5):144-149 (1991); and Manz et at., Sensors and Actuators B (Chemical) B1(1-6):249-255 (1990). The use of micromachining techniques to fabricate miniaturized separation devices on silicon or borosilicate glass chips can be found in U.S. Pat. Nos. 5,194,133 to Clark et al.; 5,132,012 to Miura et al.; in 4,908,112 to Pace; and in 4,891,120 to Sethi et al.
Because electrophoretic techniques are based on the effect of electric fields on charged particles, another approach to improve performance of electrophoretic systems is by obtaining better interaction between an electric field and the molecules of interest. PCT Publication No. WO 93/25899 describes a technique involving a time-varying field strength that may progressively increase or decrease as a function of time. One electrode each is located at each end of a electrophoretic capillary to provide the electric field. However, in such a system, high voltage is needed to drive the target substances (negatively charged DNA molecules) through the capillary.
U.S. Pat. No. 5,328,578 to Gordon discloses a capillary electrophoresis system utilizing a square ring capillary. The capillary has a hair-pin bend at each corner of the square. An opening at each bend permits fluid and electrical coupling with electrolyte outside the capillary. By switching from applying a voltage differential between selected corners, a sample is caused to repeatedly traverse the ring until satisfactory resolution has been achieved. However, to provide a high electric field in this system, the voltage differential between the electrodes still have to be large. Furthermore, it is necessary to estimate when the sample is between the corners so that the time for switching can be determined.
U.S. Pat. No. 5,126,022 to Soane et al. discloses a technique for moving charged molecules through a medium by the application of a plurality of electrical fields. A large number of electrodes are arranged along a trench or cylinder filled with medium to generate a traveling electrical wave which moves in a single direction along the trench or cylinder. To effectively use such a system, sophisticated computer equipment may be needed to move the electrical waves along the trench or cylinder.
The devices of U.S. Pat. Nos. 5,328,578 and 5,126,022 all involve relatively large conduits containing medium and are unrelated to miniaturized systems. To solve the problems in prior art electrophoresis techniques, the present invention provides electrophoretic systems capable of using easily controlled, low voltage power supply to achieve high electric field, especially such electrophoretic systems applicable in a miniaturize column separation system.